Review of Pharmacology - 9E (2015)

Review

ReviewofPharmacology 40. Ans. (b) Inhibiting spinal polysynaptic reflexes: (Ref: KDT 6/e p348) • Centrally acting muscle relaxants reduce skeletal muscle tone by a selective action in the cerebrospinal axis, without altering conciousness. • They selectively depress spinal and supraspinal polysnaptic reflexes involved in the regulation of muscle tone without significantly affecting monosynaptically mediated stretch reflex. • Polysnaptic pathways in the ascending reticular formation which are involved in the maintenance of wakefullness are also depressed, though to a lesser extent. • All centrally acting muscle relaxants do have some sedative property. They have no effect on neuromuscular transmission and on muscle fibres, but reduce decerebrate rigidity, upper motor neuron spasticity and hyperreflexia. 41. Ans. (c) Diazepam (Ref: KDT 6/e p396, 409, 450) Diazepam possesses following activities: • Muscle relaxing • Anticonvulsant • Antianxiety • Sedative-hypnotic 42. Ans. (c) Rocuronium (Ref: Pharmacology for Nurse Anaesthesiology/110) • Rocuronium causes pain on injection. It can be minimized by alkalinizing the solution. • Propofol is also responsible for pain on injection • Remember, post-operative muscular pain is caused by succinylcholine and post-operative muscle rigidity is caused by fentanyl group of drugs. 43. Ans. (b) It causes less release of histamine (Ref: Miller’s 7/e p869) Anaesthesia • Both atracurium and cis-atracurium are non-depolarizing neuromuscular blockers. • Both of these are intermediate acting agents (both have same duration of action). • Both of these agents are cardiostable • Atracurium has faster onset of action as compared to cis-atracurium. • Both are eliminated by Hoffman’s elimination. Atracurium is also metabolized by liver to some extent and result in production of a metabolite laudanosine that can cause CNS toxicity including seizures. On the other hand cis-atracurium is almost completely eliminated by Hoffman’s elimination and produce negligible laudanosine. • Major advantage of cis-atracurium over atracurium is that the former do not release histamine. Note: Only cis-atracurium and doxacurium are the drugs in this category (whose name ends with curium) that donot release histamine. 428 44. Ans. (a) Atracurium (Ref: Miller 7/e p880) Both atracurium and cis-atracurium are eliminated by Hoffman’s elimination. Atracurium is also metabolized by liver to some extent and result in production of a metabolite, laudanosine that can cause CNS toxicity including seizures. On the other hand cis-atracurium is almost completely eliminated by Hoffman’s elimination and produce negligible laudanosine. 45. Ans. (a) Mu (Ref: Miller 7/e p781) Truncal rigidity caused by highly lipid soluble opioids like fentanyl is supraspinal in origin. It is mainly caused by stimulation of mu receptors whereas kappa and delta receptors tend to reduce the rigidity. 46. Ans (b) Phase II blockade (Ref: Wiley 7/584-586, Lee 12/223) Succinylcholine produces a characteristic depolarizing block that is associated with absence of fade in response to trainof-four and titanic stimulation, the absence of post-tetanic facilitation and increased block in the presence of anticholinesterase drugs. The type of block may change into a non-depolarizing type following prolonged administration of the drug (phase II block). Transition from a depolarizing to phase II block is gradual and usually occurs after administration of 7-10 mg/kg of succinylcholine. 47. Ans. (b) Hyperkalemia (Ref: Katzung 11/e p460) Succinylcholine can cause hyperkalemia especially in patients with nerve and muscle disorders. Therefore it is contraindicated in patients with nerve diseases (like paraplegia, hemiplegia and Guillain barre syndrome) and muscle diseases (muscular dystrophy, myasthenia gravis, crush injury, burns and rhabdomyolysis). 48. Ans. (a) Atracurium (Ref: Katzung 11/e p456) Atracurium and cis-atracurium are degraded spontaneously by Hoffman’s elimination. These do not require liver or kidney for elimination and thus are muscle relaxant of choice in a patient with renal and hepatic dysfunction. • Other drugs mentioned in the question are metabolized by liver and thus should be avoided in hepatic failure. https://kat.cr/user/Blink99/

Anaesthesia 49. Ans. (b) Meprobamate (Ref: Goodman and Gilman 11/e p422) Meprobamate was used as a CNS depressant drug but is rarely indicated now due to its addictive properties. It is a metabolite of carisoprodol, which is used as a centrally acting skeletal muscle relaxant. 50. Ans. (a) Atracurium (Ref: Katzung 11/e p453) Atracurium is eliminated by Hoffman’s elimination i.e. it does not require liver or kidney. It is the muscle relaxant of choice in hepatic and renal failure. 51. Ans. (a) Azathioprine (Ref: Harrison 17/e p2677, Ajay yadav 2/e p94) • ‘Azathioprine is used for treatment of myasthenia gravis’ Drugs that may exacerbate myasthenia gravis and potentiate the action of non-depolarizing muscle relaxants are: • Antibiotics –– Aminoglycosides e.g Streptomycin –– Tetracyclines –– Quinolones e.g ciprofloxacin –– Macrolides e.g erythromycin • Non-depolarizing muscle relaxants e.g d-Tubocurarine • Beta-blockers like propanolol, atenolol, metoprolol • Local anaesthetics • Botulinum toxin • Quinine derivatives like quinine, quinidine, chloroquine, mefloquine • Magnesium • Penicillamine 52. Ans. (b) Rapacuronium (Ref: Miller’s anaesthesia 5/e p892; Drugs and equipment in Anaesthesia 5/e p78 Arun Kumar Paul) • Among the given options Rapacuronium is the shortest acting drug. • Rapacuronium has been withdrawn from the market because it produces intense bronchospasm in a significant number of patients. • Mivacurium is shortest acting NDMR. • SCh is shortest acting muscle relaxant. 53. Ans. (a) Inhibiting nicotinic receptors at myoneural junction (Ref: Katzung 10/e p429; KDT 6/e p342) D-tubocurarine is a skeletal muscle relaxant that acts by competitive inhibition of NM receptors at neuron-muscular junction. 54. Ans. (a) Cis-atracurium (Ref: Katzung 9/e p432;KDT 6/e p345) Atracurium and cis-atracurium are muscle relaxants of choice for renal and hepatic failure patients. 55. Ans. (b) Preventing the K + efflux from the cell (Ref: Katzung 10/e p436;KDT 6/e p99-101) Neostigmine is an anti-cholinesterase. It inhibits the breakdown of ACh at the motor end plate. This results in the increased activity of ACh that causes depolarization of motor end plate by opening Na + channels (increasing the influx of Na + ). It possesses some direct agonistic activity on NM receptors resulting in depolarization. In addition, a minor effect to increase the release of ACh at motor end plate is also present. 56. Ans. (b) Succinylcholine (Ref: KDT 6/e p343, 344) General Anaesthesia Pharmacology • Succinylcholine is a depolarizing neuromuscular blocker. In contrast to ganglionic blocking properties of competitive neuromuscular blockers (like d-TC), it stimulates the ganglia. • Initially bradycardia is seen due to stimulation of parasympathetic ganglion which is followed by tachycardia and hypertension due to stimulation of sympathetic ganglia. • Dopamine and isoprenaline possess b1 agonistic activity and thus can cause tachycardia. • Midazolam is a benzodiazepine. It does not affect CVS at therapeutic dose but produces bradycardia at toxic levels. 57. Ans. (a) Chloroform; (d) Halothane (Ref: Lee 12/e p167, KDT 6/e p372; Ajay yadav 2/e p61,66) • Masive liver necrosis following halothane anaesthesia is seen in some cases. • N 2 O is nontoxic to liver, kidney and brain. • Ether doesnot sensitize the heart to Adr and is not hepatotoxic. • Enflurane is eliminated mostly via the lungs, although about 3% is metabolised in body and resultant fluoride ions are excreted by kidney. Hepatic necrosis is seen in very rare instances. (Lee/165) • If chloroform is given for long period, liver damage occurs (Parikh 5/e p877) 429 https://kat.cr/user/Blink99/